Acute and Chronic Pancreatitis

Prepared and Presented by Jon Manocchio, Pharm D Blanchard Valley Hospital PGY-1 Resident

Objectives

List common causes of acute and chronic pancreatitis Describe the pathophysiology of acute and chronic pancreatitis Differentiate the signs and symptoms of acute from chronic

pancreatitis Discuss the general approach to treatment of acute and chronic

pancreatitis Describe why patients with acute pancreatitis have oral intake

discontinued temporarily Identify when it may be appropriate to prescribe empiric

antibiotics in acute pancreatitis Discuss the use of octreotide in the treatment of acute

pancreatitis Develop a plan for the appropriate administration of pancreatic

enzyme supplementation in patients with chronic pancreatitis

Background

Endocrine Function Iselets of Langerhans Insulin

Glucagon

Somatostatin

Maintenance of blood glucose

Disease caused by dysfunction Diabetes mellitus Type 1

Type 2

Background

Exocrine Function Acinar and Ductal cells Secrete 2.5 L of fluid per day Water

Electrolytes

Pancreatic enzymes

Aid in metabolism

Neutralize gastric acid Appropriate pH for enzyme activity

Pancreatic ducts carry pancreatic juice to the duodenum

Background

Major exocrine enzyme groups Amylolytic Digestion of starches

Lipolytic Breakdown of lipids (cholesterol, TG, etc)

Proteolytic Digest proteins into amino acids

Nucleolytic Breakdown nucleic acids

Other

Case Introduction

Introduction

Define Pancreatitis

Inflammation

Regional involvement

Acute Pancreatitis (AP)

Self-limiting with spontaneous resolution

Progression to chronic pancreatitis

Chronic Pancreatitis (CP)

Long-standing inflammation

Loss of function

“Classic Triad” of progression

Epidemiology

Less than 1% of people will develop AP

Approximately 6/100,000 people will develop CP

Peak incidence age 35-54

85% of cases occur in men

Men: due to alcohol

Women: due to gallstones

Acute Pancreatitis

Etiology

Most common causes

1) Gallstones

2) Alcoholism (elevated TGs)

Other causes

ERCP

End-stage kidney disease

Cigarette smoking

Medications

Risk Factors

Various

Structural

Toxins

Infections

Metabolic

Genetic

Medications

Iatrogenic

Kidney Disease

Trauma

Vascular

Idiopathic

Pathophysiology

Premature activation Trypsinogen to trypsin

Leads to activation of other digestive enzymes

Autodigestion of the pancreas and surrounding areas

Immune response to inflammation

SIRS

Possible infection

Correlation with extremely elevated TG

Presentation and Symptoms

Varies based on severity

Symptoms

Abdominal pain (95%)

Knife-like

Nausea and Vomiting (85%)

Signs

Epigastric tenderness

Laboratory Results

LFT’s (inc) TGs (inc) Amylase (inc) Lipase (inc)

Complications

Local Complications Fluid retention (pleural space) Pancreatic necrosis Infection

15-30% of those with pancreatic necrosis

Abscess

Systemic Complications Cardiovascular Renal Pulmonary (ARDS) Metabolic Hemorrhagic Central Nervous System Long-term complications

Diagnosis

Based on signs and symptoms Abdominal Pain

Increased Amylase

Increased Lipase

Use of CECT

History and patient work-up Presence of gallstones

Alcoholism

Medication Use

Disease Severity DIAGNOSIS

Age > 55 yo

WBC > 16,000/mcL

Glucose > 200mg/dL

LDH > 350 IU/L

AST > 250 IU/L

DEVELOPED (48 HRS)

Hematocrit fall > 10%

BUN rise > 5mg/dL

Ca++ < 8mg/dL

Arterial PO2 < 60 mmHg

Base deficit > 4 mEq/L

Est Fluid Sequestration > 6L

MORTALITY RATES

Number of Criteria Mortality

0-2 1%

3-4 16%

5-6 40%

>7 100%

Ranson Criteria

Goals of Therapy

Relieve abdominal pain

Relieve nausea

Replace fluids

Correct electrolyte, glucose, and lipid imbalances

Minimize systemic complications

Prevent infection (when appropriate)

NPO

Treatment

Supportive Care Abdominal pain Hydromorphone 0.5mg IV q3h PRN Meperidine Morphine

Nausea Ondansetron 4mg IV q6h PRN Promethazine 12.5-25mg IM/PO q4-6h PRN

Nutrition Begin oral feeding when bowel sounds are

present and pain has been resolved Utilize enteral feeding if oral feeding is expected

to be held for > 7 days

Treatment

Supportive Care IV fluids Plays a major role in improving prognosis 0.9% NS run continuously

Correct electrolyte deficiencies Calcium, Potassium, and Magnesium

Correct hyperglycemia Insulin

Necrotizing Pancreatitis may require antibiotics Not recommended to use as prophylaxis If infectious Imipenem/cilastatin 500mg IV q8h Ciprofloxacin or levofloxacin + metronidazole

Treatment

Limit Systemic Complications

Medications that fail to show benefit

Proton Pump Inhibitors

H2 Antagonists

Corticosteroids

Protease Inhibitors (aprotinin)

Prophylactic antibiotics

Somatostatin or Octreotide

Supportive Care

Monitoring

Hydration status

Electrolytes

Calcium, Potassium, Magnesium

Pain control

Nutritional status

Severe acute pancreatitis

Many different monitoring parameters

Prognosis

Course of disease Transient disorder Self-limiting and subsides in 3-5 days Mortality increases with unfavorable signs

Severe necrotizing disease 10% mortality rate 30-40% mortality rate with infected necrosis

Mortality During the first few days SIRS Multi-organ failure

Thereafter Infected necrosis, pan. abscess, and sepsis

Chronic Pancreatitis

Etiology

Most common cause Chronic alcohol consumption (alcoholism)

70-80% of cases Idiopathic

20% of cases Rare causes

10% of cases

Genetics Three genes

Catatonic trypsinogen (PRSS1) Serine protease inhibitor Kazal type 1 (SPINK1) Cystic fibrosis transmembrane conductance

regulator (CFTR)

Risk Factors

M-ANNHEIM Multiple risk factors

Alcohol

Nicotine

Nutritional factors

Heredity factors

Efferent duct factors

Immunologic factors

Miscellaneous and rare factors

Pathophysiology

Exact mechanism is unknown

Proposed theories

Oxidative stress

Toxic metabolite

Ductal obstruction

Periductal necrosis

Presentation and Symptoms

“Classic Triad” Chronic abdominal pain Steatorrhea Diabetes mellitus

Signs Malnutrition Abdominal mass Possible jaundice

Laboratory Results May only be abnormal during an acute attack Glucose (inc) CBC

Diagnosis

Based on signs and symptoms

Presence of the “Classic Triad”

Imaging studies

Gold standard: ERCP

Also EUS

History and patient work-up

Presence of gallstones

Alcoholism

Medication Use

Acute pancreatitis seldom indicates progression to chronic pancreatitis

Goals of Therapy

Relieve abdominal pain

Treatment of associated complications Steatorrhea

Malabsorption

Diabetes Mellitus

Loss of endocrine function

Improve quality of life

Treating secondary disorders Depression

Malnutrition

Treatment

Lifestyle modifications

Abstain from alcohol

Smoking cessation

Eat small, frequent meals

Reduce dietary fat intake

0.5g/kg/day

Treatment

Specific Regimens Abdominal Pain Non-opioid analgesics APAP 500mg QID maximum (with alcohol)

NSAIDS normal dosing patterns

Tramadol 50-100mg q4-6h

Non-opioid analgesics + pancreatic enzymes

Opioid analgesics Codeine 30-60mg PO q6h

Hydrocodone 5-10mg PO q4-6h

Hydromorphone 0.5-1mg PO q4-6h

Treatment

Specific Regimens Malabsorption Begin when steatorrhea is present and

weight loss occurs

Creon 6,000, Creon 12,000, Creon 24,000 Varies based on lipase content

Administer with or just after a meal

May be used with a PPI or H2A to allow for greater availability (gastric pH prevents release)

Diabetes Insulin remains the gold standard

Monitoring

Pain Control

Constipation

Weight

Stool frequency

Blood glucose

Prognosis

Life expectancy 10 year survival rate

70%

20 year survival rate

45%

Morality Cardiovascular disease

Infection

Malignancy

Pancreatic Cancer 15 times more likely with alcoholic pancreatitis

Case Conclusion

Conclusion

Pancreatitis can be an acute or a chronic disease

Limiting alcohol intake greatly reduces the chances of developing pancreatitis

The exact pathophysiological causes of each is ambiguous

A person with acute pancreatitis will not necessarily develop chronic pancreatitis

The gold standard for treatment is supportive care as well as pain management

Other treatment modalities have vague evidence with limited success

Patients should be monitored frequently to identify any recurrent exacerbations or complications associated with each disease state

Questions?

References 1) Banks PA and Freeman ML. Practice Guidelines in Acute Pancreatitis. Am

J Gastroenterol. 2006; 101: 2379-2400.

2) Bolesta S, Montgomer PA, “Chapter 46. Pancreatitis” (Chapter). DiPiro JT, et al: Pharmacotherapy: A Pathophysiologic Approach, 8e: http://www.accesspharmacy.com.polar.onu.edu

3) Fauci AS, et al, “Chapter 313. Acute and Chronic Pancreatitis” (Chapter).

Fauci et al: Harrison’s Principles of Internal Medicine, 17e: http://www.accesspharmacy.com.onu.edu

4) Giuliano CA, et al. Pancreatic Enzyme Products: Digesting the Changes.

Ann Pharmacother. 2011; 45: 658-65. 5) McPhee SJ et al, “Differential Diagnosis and Diagnostic Algorithms”

(Chapter). Nicoll D, McPhee SJ, Pignone M: Pocket Guide to Diagnostic Tests, 5e: http://www.accesspharmacy.com.polar.onu.edu

Previous Test Questions

Clinically, which opioid analgesic is most often used in the inpatient setting to control the pain associated with pancreatitis? Morphine

Hydromorphone

Meperidine

Oxycodone

Fentanyl

Previous Test Questions

Which statement adequately describes the use of antibiotics with pancreatitis?

Antibiotics should always be used as prophylaxis

Antibiotics should be used during pancreatitis only when a culture and sensitivity is available

Antibiotic therapy should only be initiated after pain is completely controlled

Antibiotics should only be initiated if infection is suspected, as in the development of sepsis

Antibiotics are contraindicated for use at anytime during pancreatitis

Previous Test Questions

A 73yom presents to the ED complaining of epigastric pain and nausea for the past 10 days. His history is significant for CP, HTN, DM, and alcoholism. Lab results are wnl except for glucose (187), potassium (3.2) and sCr (1.6). Home medications were unable to be obtained. Based on this information, which of the following options would be an appropriate to initiate?

Begin 0.9%NS @150 mL/hr

Begin hydromorphone 0.5mg IV q3-4h

Begin imipenem/cilastatin 500mg IV q8h

A and B

A, B, and C

Previous Test Questions

Which enzyme is responsible for converting trypsinogen to trypsin?

Enterokinase

CCK

Secretin

Amylase

VIP

Previous Test Questions

Which of the following is NOT associated with the “Classic Triad” of chronic pancreatitis?

Epigastric Pain

Diarrhea

Steatorrhea

Diabetes mellitus

None of the above, all of these are associated with the “Classic Triad”